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The Body Covers: The 7th Annual Clinical Care Options for HIV Symposium
Break-Out Session: Emerging Issues in Opportunistic Infections

June 1997

A note from The field of medicine is constantly evolving. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

When this year's symposium was first planned, this break-out session was organized around what were then felt to be important "emerging" issues in opportunistic infections. Since that time, however, the success of Highly Active Antiretroviral Therapy (HAART) has made many of those questions less interesting. For example, one of the case studies that was to have been discussed at this session involved a case of fluconazole-resistant candidiasis, certainly one of the "hot topics" a year ago. A show of hands (or lack thereof) among audience members confirmed the speakers' impression that this is a problem that seems to be disappearing, as antiretroviral therapy becomes more effective.

Thus, the original agenda was abandoned, and much of the discussion focused on real-world applications of the concepts posed by Clifford Lane in his talk (reported here) on immune reconstitution. Given what we know about the selective reexpansion of memory CD4 cells over naive CD4 cells, must we always continue prophylaxis after effective antiretroviral therapy has resulted in a large increase in CD4 cell count?

The effect of HAART on the CMV disease may be the best studied association between drug-induce immune reconstitution and opportunistic complications. Studies presented at the Retrovirus meeting in Washington earlier this year included:

  • Ruane PJ: Home care referrals for new CMV disease have dropped by 90%.
  • Mars ME: The incidence in CMV and MAC has dropped from 11% to 3% in 1996.
  • Gilquin J: CMV disease was reported in eight patients after starting HAART.
  • Jacobsen MA: CMV was reported in 5 patients with CD4 counts over 200, within 8 weeks after starting HAART.
  • Michelet C: 4 out of 50 patients starting HAART developed CMV disease (mean CD4 count 41)

These data show that although effective antiretroviral therapy clearly reduces the incidence of CMV disease and other opportunistic complications, it does not completely eliminate the risk. These reports, together with the immunologic data presented by Clifford Lane, have led to recommendations from the USPHS that prophylaxis decisions be based on the nadir of the CD4 count, and that prophylaxis be continued despite increases in CD4 due to antiretroviral therapy.

There was considerable discussion about this recommendation and how rigorously it needs to be followed in clinical practice. The experts agreed that there is currently no way to measure the specificity of memory and naive CD4 cells, so there is no way to determine whether a patient retains immunity to individual pathogens. Clearly, the risk is continuous, not dichotomous, and decisions need to based on a balance between the risk to the patient of stopping prophylaxis versus the costs to the patient of continuing it.

One clinician reported that he had stopped PCP prophylaxis in numerous patients after their CD4 counts had risen well above 200, and that he had seen no cases of PCP in those patients. However, others pointed out that most of the opportunistic infections for which reductions in incidence have been seen have been later stage infections such as MAC and CMV, rather than infections associated with less severe immunodeficiency. Furthermore, PCP prophylaxis is inexpensive, simple, and well-tolerated for patient who can take TMP/SMX or dapsone. The benefit of stopping prophylaxis in such patients is marginal. In contrast, the benefits of stopping MAC prophylaxis, or especially CMV prophylaxis when it is used, are considerably greater given the greater cost and toxicity of the agents used to prevent these infections. Finally, stopping PCP prophylaxis may a much riskier strategy than stopping MAC prophylaxis. In the latter case, the risk is that patients will develop MAC, which is readily treatable. In the former case, however, there is a much greater risk of significant morbidity or mortality should the patient develop PCP.

Clearly, we need to redefine the natural history of HIV disease in this new era in order to make educated decisions. Just as we began using PCP prophylaxis based on MACS data demonstrating a greatly increased risk in patients with CD4 counts under 200, we need similar data to show us what happens to patients who increase their CD4 counts as a result of therapy. Further analysis of data from ACTG 320, the large trial of AZT/3TC vs. AZT/3TC/indinavir in patients with advanced disease, may help to better define the risk of specific opportunistic infections in the era of HAART. Data from the many large clinical databases will also prove useful. As helpful as the immunologic data on what happens to specific CD4 phenotypes, it will never substitute for larger-scale, "real world" data on what happens to patients. Until we have natural history data, clinicians should consider the current guidelines, and make decisions using their best clinical judgment.

A note from The field of medicine is constantly evolving. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

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Please note: Knowledge about HIV changes rapidly. Note the date of this summary's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this summary. For a complete listing of our most recent conference coverage, click here.